Inflammation has been implicated in a number of neurodegenerative disorders (e.g., amyotrophic lateral sclerosis (ALS) and multiple sclerosis). For example, increased inflammatory responses have been observed in both human ALS patients and animal models of ALS (McGreer et al., Muscle Nerve 26:459-470, 2002; Beers et al., Proc. Natl. Acad. Sci. U.S.A. 105:15558-15563, 2008; Banerjee et al., PLoS ONE 3:e2740, 2008; Chiu et al., Proc. Natl. Acad. Sci. U.S.A. 105:17913-17918, 2008; Chiu et al., Proc. Natl. Acad. Sci. U.S.A. 106:20960-20965, 2009; Beers et al., Proc. Natl. Acad. Sci. U.S.A. 103:16021-16026, 2006; Henkel et al., Ann. Neurol. 55:221-235, 2004; Meissner et al., Proc. Natl. Acad. Sci. U.S.A. 107:13046-13050, 2010). It has been reported that both microglia and astrocytes are activated in the central nervous system in a mouse model of familial ALS (Alexianu et al., Neurology 57:1282-1289, 2001; Hall et al., Glia 23:249-256, 1998), and that natural killer cells and peripheral T-cells infiltrate the spinal cord during neurodegenerative disease progression in a mouse model of ALS (Chiu et al., Proc. Natl. Acad. Sci. U.S.A. 105:17913-17918, 2008).
In the peripheral nervous system, degeneration of peripheral motor axons is an early and significant pathological feature in ALS patients and in animal models of ALS, and is preceded by the recruitment and activation of macrophages (Chiu et al., Proc. Natl. Acad. Sci. U.S.A. 106:20960-20965, 2009). A specific monocyte subset (Ly6CHi) in mice participates in tissue damage and disease pathogenesis in a mouse models of multiple sclerosis (King et al., Blood 113:3190-3197, 2009), and these monocytes are recruited to inflamed tissues by CCL2 (Kim et al., Immunity 34:769-780, 2011; Getts et al., J. Exp. Med. 205:2319-2337, 2008).